Autoimmune diseases, e.g., multiple sclerosis (MS), insulin-dependent diabetes mellitus (IDDM), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and psoriasis represent assaults by the body's immune system which may be systemic in nature, or else directed at individual organs in the body. They appear to be diseases in which the immune system makes mistakes and, instead of mediating protective functions, becomes the aggressor (1).
MS is the most common acquired neurologic disease of young adults in Western Europe and North America. It accounts for more disability and financial loss, both in lost income and in medical care, than any other neurologic disease of this age group. There are approximately a total of 1,000,000 cases of MS in the United States and Europe.
Although the cause of MS is unknown, advances in brain imaging, immunology, and molecular biology have increased researchers' understanding of this disease. Several therapies are currently being used to treat MS, but no single treatment has demonstrated dramatic treatment efficacy. Current treatment of MS falls into three categories: treatment of acute exacerbations, modulation of progressive disease, and therapy for specific symptoms.
MS affects the central nervous system and involves a demyelination process, i.e., the myelin sheaths are lost whereas the axons are preserved. Myelin provides the isolating material that enables rapid nerve impulse conduction. Evidently, in demyelination, this property is lost. Although the pathogenic mechanisms responsible for MS are not understood, several lines of evidence indicate that demyelination has an immunopathologic basis. The pathologic lesions, the plaques, are characterised by infiltration of immunologically active cells such as macrophages and activated T cells (2).
In U.S. Pat. No. 5,219,864 some thieno[2,3-b]pyridine and thieno[3,2-b]pyridine derivatives represented by formula (A)
wherein Z represents pyridyl are claimed as immunoregulators and for the prevention and treatment of osteoporosis.
In WO 94/29295 compounds of general formula (B) are disclosed
wherein Y among others represents
viz. thieno[3,2-b]pyridine derivatives, and N represents a bicyclic heterocyclic group containing at least one nitrogen atom, R5 represents lower alkyl and R6 represents hydroxy, and which possess immunomodulating activity, anti-inflammatory activity and anti-cancer activity.